• Title/Summary/Keyword: First-line treatment

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Comparative Analysis of the Efficacy and Safety of Oxaliplatin Plus 5-Fluorouracil/Leucovorin (Modified FOLFOX6) with Advanced Gastric Cancer Patients having a Good or Poor Performance Status

  • Hacibekiroglu, Ilhan;Kodaz, Hilmi;Erdogan, Bulent;Turkmen, Esma;Esenkaya, Asim;Uzunoglu, Sernaz;Cicin, Irfan
    • Asian Pacific Journal of Cancer Prevention
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    • v.16 no.6
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    • pp.2355-2359
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    • 2015
  • Background: Combination chemotherapy of 5 fluorouracil (5-FU) and leucovorin (LV) with oxaliplatin, mainly FOLFOX regimens, has shown considerable antitumor activity and a tolerable toxicity profile in gastric cancer. The goal of this study was to retrospectively compare the efficacy and toxicity of modified FOLFOX-6 (mFOLFOX6) regimen in advanced gastric cancer (AGC) patients with good and poor performance status (PS). Materials and Methods: AGC patients receiving the mFOLFOX6 regimen including oxaliplatin $85mg/m^2$, bolus of 5-FU $400mg/m^2$ and LV $400mg/m^2$ on the first day, followed by $2400mg/m^2$ of 5- FU as a continious infusion over 46 hour for first-line treatment were eligible for the study. Results: A total 58 patients with a median age of 59.5 (32-81) were included. The median follow up of the study was 9.2 months. Thirty patients (51.7%) with an ECOG PS 0-1 were assigned to the good PS arm, while 28 patients (48.3%) with ECOG PS 2 were in the poor PS arm. Overall response rates were 36.6 and 28.8%, respectively (p=0.91). Median PFS was 6.7 and 6.3 months in good PS and poor PS arms (p=0.50) and median OS was 9.6 and 10.4 months (p=0.55). As compared with good PS arm, poor PS arm was associated with more grade 3-4 neutropenia and anemia. Dose reduction and dose delays were also significantly higher. Conclusions: In this study, mFOLFOX6 was similarly effective in both arms. Although hematologic toxicity was significantly higher in patients with poor PS, it remained manageable. Our results suggest that this regimen may be an effective treatment option for AGC patients with poor PS.

Combined Treatment with Stattic and Docetaxel Alters the Bax/Bcl-2 Gene Expression Ratio in Human Prostate Cancer Cells

  • Mohammadian, Jamal;Sabzichi, Mehdi;Molavi, Ommoleila;Shanehbandi, Dariush;Samadi, Nasser
    • Asian Pacific Journal of Cancer Prevention
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    • v.17 no.11
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    • pp.5031-5035
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    • 2016
  • Docetaxel, recognized as a stabilizing microtubule agent, is frequently administrated as a first line treatment for prostate cancers. Due to high side effects of monotherapy, however, combinations with novel adjuvants have emerged as an alternative strategy in cancer therapy protocols. Here, we investigated the combined effects of stattic and docetaxel on the DU145 prostate cancer cell line. Cytotoxicity was evaluated by MTT assay. To understand molecular mechanisms of stattic action, apoptotic related genes including Bcl-2, Mcl-1, Survivin and Bax were evaluated by real-time RT-PCR. Alteration in the expression of pro-apoptotic Bax and anti-apoptotic Bcl-2 genes and Bax/Bcl-2 ratio were investigated via the $2^{{\Delta}{\Delta}CT}$ method. The $IC_{50}$ values for docetaxel and stattic were $3.7{\pm}0.9nM$ and $4.6{\pm}0.8{\mu}M$, respectively. Evaluation of key gene expression levels revealed a noticeable decrease in antiapoptotic Bcl-2 and Mcl-1 along with an increase in pro-apoptotic Bax mRNA levels (p<0.05). Our results suggest that combination of a STAT3 inhibitor with doctaxel can be considered as a potent strategy for induction of apoptosis via increasing Bax mRNA expression.

Vitamin D Proliferates Vaginal Epithelium through RhoA Expression in Postmenopausal Atrophic Vagina tissue

  • Lee, Arum;Lee, Man Ryul;Lee, Hae-Hyeog;Kim, Yeon-Suk;Kim, Jun-Mo;Enkhbold, Temuulee;Kim, Tae-Hee
    • Molecules and Cells
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    • v.40 no.9
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    • pp.677-684
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    • 2017
  • Postmenopausal atrophic vagina (PAV) is the thinning of the walls of the vagina and decreased lugae of the vagina. PAV is caused by decreased estrogen levels in postmenopausal women. However, the harmful effects of hormone replacement therapy (HRT) have resulted in considerable caution in its use. Various estrogen agonist treatment options are available. Vitamin D is influences the regulation of differentiation and proliferation of various cells, especially tissues lining stratified squamous epithelium, such as the vaginal epithelium. In this study, we hypothesized that vitamin D could provide an alternative and a safe treatment option for PAV by promoting the proliferation and differentiation of the vaginal epithelium. Thirty six patients were enrolled in this case-control study. Vitamin D associated proteins in a vitamin D and sex hormone treated vaginal epithelial cell line as well as normal and PAV tissues were measured. To confirm of cell-to-cell junction protein expression, cell line and tissue studies included RT-PCR, immunohistochemistry staining, and immunoblot analyses. The expression of cell-to-cell junction proteins was higher in women with symptoms of atrophic vagina tissue compared to women without the symptoms. Vitamin D stimulated the proliferation of the vaginal epithelium by activating p-RhoA and Erzin through the vitamin D receptor (VDR). The results suggest that vitamin D positively regulates cell-to-cell junction by increasing the VDR/p-RhoA/p-Ezrin pathway. This is the first study to verify the relationship of the expression of RhoA and Ezrin proteins in vaginal tissue of PAV.

Chemopreventive Actions of Blond and Red-Fleshed Sweet Orange Juice on the Loucy Leukemia Cell Line

  • Dourado, Grace KZS;Stanilka, Joy M;Percival, Susan S;Cesar, Thais B
    • Asian Pacific Journal of Cancer Prevention
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    • v.16 no.15
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    • pp.6491-6499
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    • 2015
  • Background: Red-fleshed sweet orange juice (ROJ) comes from a new variety of citrus cultivated in Brazil that contains high levels of ${\beta}$-carotene and lycopene, and similar amounts of hesperidin (HSP) and nutrients, equivalently to blond orange juice (BOJ). Such bioactive compounds are associated with chemopreventive actions in several cancer cell lines. The purpose of this study was to examine the cytotoxicity, cell cycle, apoptosis, and cytokine secretion after BOJ, ROJ, and HSP treatment of a novel T acute lymphoblastic leukemia cell line, Loucy. Materials and Methods: Loucy cells were incubated for 24-h with BOJ, ROJ, and HSP, and the viability was measured using trypan blue. Cell cycling and apoptosis were assessed by propidium iodide (PI) and annexin V-FITC/PI flow cytometry, respectively. Secretion of cytokines $IL-1{\alpha}$, $IL1-{\beta}$, IL-2, IL-4, IL-6, IL-10, IL-17A, $IFN{\gamma}$, $TNF{\alpha}$, $TGF{\beta}$, $MIP{\alpha}$, and $MIP{\beta}$ was determined by ELISA array. Results: BOJ and ROJ treatments promoted Loucy cell cytotoxicity. Additionally, BOJ induced cell cycle arrest in the G0/G1 phase, and decreased the cell accumulation in the G2/M. ROJ decreased only the G0/G1 fraction, while HSP did not change the cell cycle. BOJ led to apoptosis in a different fashion of ROJ, while the first treatment induced apoptosis by increase of late apoptosis and primary necrotic fractions, the second increased early and late apoptosis, and primary necrotic fraction compared to positive controls. HSP had no effect on apoptosis. IL-6 and IL-10 were abrogated by all treatments. Conclusions: Taking together, these results suggest potential chemopreventive effects of BOJ and ROJ on Loucy cells.

Antiproliferative Evaluation and Apoptosis Induction in MCF-7 Cells by Ziziphus spina christi Leaf Extracts

  • Farmani, Fatemeh;Moein, Mahmoodreza;Amanzadeh, Amir;Kandelous, Hirsa Mostafapour;Ehsanpour, Zahra;Salimi, Mona
    • Asian Pacific Journal of Cancer Prevention
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    • v.17 no.1
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    • pp.315-321
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    • 2016
  • Background: Herbal medicine has becoming a potential source of treatment for different types of cancer including breast cancer. It has been shown that plants from the family Rhamnaceae possess anticancer activity. Objective: In this study, we determined the antiproliferative influence of Ziziphus spina christi- a species from this family- on the MCF-7 (human breast adenocarcinoma) cell line. Materials and Methods: The cytotoxicity of the total extract, ethanol, ethanol-aqueous (1:1) as well as aqueous fractions of Ziziphus spina christi leaves was evaluated through MTT assay against MCF-7 cell line. Cell cycle inhibition and apoptosis induction were assessed by flowcytometry cycle RNase/PI analysis and Annexin V-FLUOS, respectively. Apoptosis was also analyzed by immunoblotting assay. Results: Our results indicated that the ethanolic fraction had the lowest $IC_{50}$ value (0.02 mg/ml), induced cell cycle arrest at the G1/S phase as well as apoptosis after a 48h of treatment. Conclusions: This is the first report on anticancer effect of Ziziphus spina christi ethanolic fraction on breast cancer cells, providing a scientific basis for its utility in traditional medicine. However, further in-depth studies are needed to confirm the precise mechanisms.

A Case of Bilateral Gynecomastia Associated with Isoniazid (Isoniazid를 포함한 항결핵약제 투여 후 발생한 여성형 유방 증례 1예)

  • Heo, Eun Young;Jeong, Ina;Lee, Jae Seok;Lee, Chang Hoon;Chung, Hee Soon;Kim, Deog Kyeom
    • Tuberculosis and Respiratory Diseases
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    • v.65 no.4
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    • pp.308-312
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    • 2008
  • Gynecomastia is a benign enlargement of the male breast attributable to proliferation of the ductal elements. Gynecomastia has been rarely reported as an adverse effect of isoniazid therapy. We report the case of a 35-year-old man who was prescribed with isoniazid, rifampicin, ethambutol and pyrazinamide to treat pulmonary and lymphatic tuberculosis. After five months of treatment, the patient complained of painful engorgement in the bilateral breasts and the presence of male gynecomastia was confirmed with a physical examination and radiographical methods. The serum level of estradiol was also increased. Common causes of male gynecomastia were excluded through history taking and the laboratory findings. The anti-TB drugs were changed to a second line regimen due to radiographical progression and the intolerance of the patient to gynecomastia. Gynecomastia was relieved very slowly and a tender subareolar palpable mass decreased in size and consistency over five-month period after stopping the probable causative drug, isoniazid. From a review of the literature, gynecomastia has been shown to be a side effect of treatment with first line anti-tuberculosis drugs, and especially with isoniazid. We report the rare case.

The Clinical Efficacy and Safety of Four-Weekly Docetaxel as First-Line Therapy in Elderly Lung Cancer Patients with Squamous Cell Carcinoma

  • Choi, Jong Hyun;Choi, Juwhan;Chung, Sang Mi;Oh, Jee Youn;Lee, Young Seok;Min, Kyung Hoon;Hur, Gyu Young;Shim, Jae Jeong;Kang, Kyung Ho;Lee, Hyun Kyung;Lee, Sung Yong
    • Tuberculosis and Respiratory Diseases
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    • v.82 no.3
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    • pp.211-216
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    • 2019
  • Background: Docetaxel is one of the standard treatments for advanced non-small cell lung cancer. Docetaxel is usually administered in a 3-week schedule, but there is significant toxicity. In this phase II clinical study, we investigated the efficacy and safety of a 4-weekly schedule of docetaxel monotherapy, as first-line chemotherapy for advanced squamous cell carcinoma in elderly lung cancer patients. Methods: Patients with stage IIIB/ IV lung squamous-cell carcinoma age 70 or older, that had not undergone cytotoxic chemotherapy were enrolled. Patients received docetaxel $25mg/m^2$ on days 1, 8, and 15, every 4 weeks. Primary endpoint was the objective response rate (ORR). Secondary endpoints were progression-free survival (PFS), overall survival (OS), and toxicity profiles. Results: A total of 19 patients were enrolled. Among 19 patients, 17 were for evaluated efficacy and safety. In the intent-to-treat population, ORR and disease control rate (DCR) were 11.8% and 47.1%, respectively. In the response evaluable population, ORR was 16.7% and DCR was 66.7%. Median PFS and OS were 3.1 months and 3.3 months, respectively. There were three adverse grade 3/4 events. Grade 1 neutropenia was reported in one patient. Conclusion: Our data failed to demonstrate efficacy of a 4-weekly docetaxel regimen, in elderly patients with a poor performance status. However, incidence of side effects, including neutropenia, was lower than with a 3-week docetaxel regimen, as previously reported.

Recent Advances in Immune-based Therapy for Hepatocellular Carcinoma (간세포암종의 면역 기반 항암치료의 최신 지견)

  • Kyung Won Park;Tae Hoon Park;Eun Ji Jang;Pil Soo Sung
    • Journal of Digestive Cancer Research
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    • v.12 no.2
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    • pp.115-130
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    • 2024
  • The incidence of hepatocellular carcinoma (HCC) is continuously increasing worldwide, with approximately 1 million new cases expected annually by 2025. Data from the Korean Central Cancer Registry in 2023 revealed that the survival rate of patients with HCC was only 40%, unlike patients with other major cancers with a 5-year survival rate of up to 80%, highlighting the need for improved outcomes. The prognosis of HCC significantly changed following research on immune checkpoint inhibitors (ICIs). Several studies have demonstrated that the overall survival of patients treated with first-line combination therapies, such as atezolizumab (anti-PD-L1) and bevacizumab (anti-VEGF) or durvalumab (anti-PD-L1) and tremelimumab (anti-CTLA-4), was higher than that of patients treated with sorafenib. Research to identify biomarkers that can predict ICI responses is ongoing, enabling the selection of suitable patients before drug initiation. Moreover, studies of the tumor microenvironment in HCC enhance our understanding of immune responses, helping us identify new therapeutic strategies. Additionally, clinical trials are being conducted for emerging immunotherapies beyond ICIs, such as adoptive cell therapy. Based on these ongoing scientific researches and the development of various therapeutic modalities, multiple options are being established for patients with HCC who do not respond well to first-line treatments. Consequently, treatment options and survival rates of patients with advanced HCC could be significantly enhanced in the future.

Clinical Outcome after Treatment with the First-line Drugs in Patients with Persistent Positive Sputum Smear and Negative Sputum Culture Results (지속적인 객담 도말양성 및 배양음성인 폐결핵환자에서 일차항결핵제로 치료종결한 후의 임상성적)

  • Kwon, Eun-Su;Lee, Jong-Youk
    • Tuberculosis and Respiratory Diseases
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    • v.51 no.4
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    • pp.325-333
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    • 2001
  • Background : This study aimed to estimate the clinical outcome and identify the characteristics of a group of patients with pulmonary tuberculosis who completed anti-tuberculosis therapy with the First-line drugs in spite of having positive smear results with negative sputum culture results over the previous six months. Method : A retrospective chart review of 21 patients who fulfilled the above criteria between 1995 and 1999 was performed. The laboratory data as well as the clinical data of the patients with positive smear results and negative culture results over a six months period were reviewed. Results : The negative conversion of sputum culture results was achieved within $1.3{\pm}1.2$ months and the negative conversion of the sputum smear results was accomplished during $9.5{\pm}3.3$ months. Chest X-rays at 5 months following the institution of anti-tuberculosis therapy from all patients revealed improvements. Four out of 21 patients(19%) relapsed during the follow up, $15.2{\pm}13.4$ months after administering anti-tuberculosis therapy for $13.3{\pm}3.1$ months. Relapses were confirmed from between 3 months and 4 months after the treatment completion. Only one of the four relapses had no past history of anti-tuberculosis therapy and the others had prior treatment twice (p<0.01). The period of anti-tuberculosis treatment was extended to a mean of $4.6{\pm}2.6$ months in 12 patients. However, prolongation of anti-tuberculosis therapy had no affect on the relapse rate (odds ratio, 95% CI 0.18, 2.15). Conclusion : Prolongation of therapy with the First-line drugs is not necessary for patients with persistently positive smear results over 6 months and negative culture results. A patient who has had prior anti-tuberculosis therapy more than twice should be paid the closest attention.

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A Study on the Feasibility of COBie to the Wastewater Treatment Plant (COBie 기반 하수처리시설 유지관리시스템 구축)

  • Choi, Jae-Ho;Um, Dong-Yong
    • KSCE Journal of Civil and Environmental Engineering Research
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    • v.34 no.1
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    • pp.273-283
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    • 2014
  • With the introduction of COBie (Construction Operation Building Exchange) in BIM technology enabling an automatic transfer of design and construction information to operation and management (O&M) phase, the BIM centric O&M management system development process has been tested on the subject of architectural types of building. However, for now, there is a need to investigate the technical feasibility of COBie application to civil structures including industrial facilities. This study takes both "O&M Guideline for Public Wastewater Treatment Plant" and a real wastewater treatment plant into account for the purpose, in which the latter is intended to supplement the result of the first. The findings are three-folds: (1) COBie, as an asset modeling, is not sufficient enough to encompass commissioning data, (2) more relevant IFC development and family library build-up useful to modeling wastewater treatment plant is imperative, and (3) well-planned coordination and organization of COBie data-set in line with O&M practice will enhance the feasibility of the COBie in industrial facilities. The result could be used for a basis study for COBie application, particularly in industrial facilities.